Project Summary Recognition of social behavior and cell-cell signaling as a ubiquitous property of bacteria revolutionized our understanding of microbiology and microbial pathogenesis. Parasitic protozoa generally are not considered in this context. Recent work however, demonstrates that the paradigm of microbes as social organisms can and should be brought to bear on questions about parasite biology, transmission and pathogenesis. African trypanosomes, e.g. Trypanosoma brucei, and related trypanosomatid parasites are responsible for substantial human suffering worldwide. T. brucei is transmitted between human hosts by tsetse flies. The parasites live in communities in which they can communicate with one another and engage in group behaviors that are not evident in individual cells, this behavior is termed ?Social Motility? (SoMo) and shows analogies to social behavior in bacteria. Studies of SoMo have generated insight into parasite development, transmission, signaling and chemotaxis. In the current proposal we will use recently developed SoMo mutants and new tools for imaging parasites in mixed populations to determine the role of social behavior and cAMP for infection of tsetse flies, define gene expression programs that govern social behavior and tsetse fly infection, and dissect mechanisms of parasite chemotaxis. We expect our studies will provide new perspectives and approaches for understanding parasite biology, which in turn are necessary to develop novel strategies for management and therapeutic intervention in parasitic disease.